Methods
A total of 969 patients hospitalized between April 2020 and January 2021 were screened in this retrospective study. Two hundred ninety-three participants with polymerase chain reaction confirmed COVID-19 were divided into the favipiravir group (n=159) and the HQ group (n=135). Patients not meeting the criteria were excluded from the study (Table-1). Finally, 101 participants in the favipiravir group and 93 in the HQ group were included in the study (Figure-1).
Healthcare system algorithms have been applied to the treatment of patients. HQ, azithromycin, and oseltamivir triple therapy were given to patients hospitalized until July 2, 2020. Afterward, algorithms switched to favipiravir and levofloxacin. The authors compared the arrhythmic adverse effects between the two groups. HQ group treatment regimen were; HQ 200 mg orally twice a day for five days, azithromycin 500 mg orally once daily for five days, and subcutaneous enoxaparin 1 mg/kg. Favipiravir group protocol was as follows; favipiravir 1600mg loading dose, 600mg twice daily for four days, levofloxacin 500 once a day for five days, and subcutaneous enoxaparin 1 mg/kg. Symptom-based medications such as ceftriaxone, paracetamol, pantoprazole, dexamethasone were given in both groups.
Demographics, clinical characteristics, laboratory data, medications, outcomes, basal and predischarge electrocardiography (ECG) were obtained from the patient data registry. Electrolyte levels that could trigger arrhythmia, troponin, D-dimer, and C-reactive protein were examined in all participants. Inpatient medications and hemodynamic parameters such as heart rate, blood pressure, and oxygen saturation were reconsidered daily. The present study was approved by the local ethics committee and the Ministry of Health Scientific Research Platform (2021-02-15T01_58_28). Written and signed informed consent was obtained from the participants.
A standard 12-lead ECG (Cardiofax m, NIHON KOHDEN Corp. Tokyo, Japan) was performed at admission and discharge. Baseline and final ECGs of the participants were compared. The following data were analyzed in the admission and predischarge ECG or ECG during the arrhythmia; rhythm, heart rate (HR), QRS duration, PR and QT interval, extrasystole, and conduction disturbance. All parameters were manually measured from an ECG by the same cardiologist. The physician employed Lead-II to analyze rhythm, QRS duration, PR, and QT interval on ECG. If lead-II was not applicable, lead-I was assessed. Bazett formula was utilized to calculate the corrected QT (QTc) interval. The QTc prolongation was defined as > 440 ms in males, >460 ms in females.
The primary analysis was an evaluation of the arrhythmogenic adverse effects of the favipiravir and HQ groups. The Shapiro-Wilk test evaluated the normal distribution of variables. Continuous and categorical variables were given as mean±SD or median (IQR) and percentage, respectively. According to the data’s distribution, the groups’ variables were compared using the student t-test or Mann-Whitney U test and the chi-square test or Fisher’s exact test. Paired samples t-test was applied to evaluate for initial and final ECG measurements within groups. Statistical analyses were undertaken using the SPSS version 22.0 software package (IBM SPSS, New York, USA) and MedCalc version 15.8 statistical software (Ostend Belgium). The statistical significance threshold was adjusted as p <0.05.